Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease

EUCLID Trial Steering Committee and Investigators, W. Schuyler Jones, Iris Baumgartner, William R. Hiatt, Gretchen Heizer, Michael S. Conte, Christopher J. White, Jeffrey S. Berger, Peter Held, Brian G. Katona, Kenneth W. Mahaffey, Lars Norgren, Juuso Blomster, Marcus Millegård, Craig Reist, Manesh R. Patel, F. Gerry R. Fowkes (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

Background: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.

Methods: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding.

Results: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months.

Conclusions: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalCirculation
Volume135
Issue number3
Early online date13 Nov 2016
DOIs
Publication statusPublished - 17 Jan 2017

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clopidogrel
Peripheral Arterial Disease
Lower Extremity
Ankle Brachial Index
Confidence Intervals
Extremities
Myocardial Infarction
Ischemia
Ticagrelor
Stroke
Hemorrhage

Keywords

  • lower extremity revascularization
  • peripheral artery disease
  • ticagrelor
  • vascular intervention

Cite this

EUCLID Trial Steering Committee and Investigators, Schuyler Jones, W., Baumgartner, I., Hiatt, W. R., Heizer, G., Conte, M. S., ... Fowkes, F. G. R. (2017). Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease. Circulation, 135(3), 241-250. https://doi.org/10.1161/CIRCULATIONAHA.116.025880
EUCLID Trial Steering Committee and Investigators ; Schuyler Jones, W. ; Baumgartner, Iris ; Hiatt, William R. ; Heizer, Gretchen ; Conte, Michael S. ; White, Christopher J. ; Berger, Jeffrey S. ; Held, Peter ; Katona, Brian G. ; Mahaffey, Kenneth W. ; Norgren, Lars ; Blomster, Juuso ; Millegård, Marcus ; Reist, Craig ; Patel, Manesh R. ; Fowkes, F. Gerry R. / Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease. In: Circulation. 2017 ; Vol. 135, No. 3. pp. 241-250.
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abstract = "Background: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.Methods: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57{\%}) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding.Results: Patients with a previous revascularization had a mean age of 66 years, 73{\%} were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95{\%} confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95{\%} CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95{\%} CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4{\%} vs 11.3{\%}; HR 1.01, 95{\%} CI 0.88-1.15; P=0.90), all-cause mortality (9.2{\%} vs 9.2{\%}; HR 0.99, 95{\%} CI 0.86-1.15; P=0.93), acute limb ischemia (2.5{\%} vs 2.5{\%}; HR 1.03, 95{\%} CI 0.78-1.36; P=0.84), or major bleeding (1.9{\%} vs 1.8{\%}; HR 1.15, 95{\%} CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months.Conclusions: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.",
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author = "{EUCLID Trial Steering Committee and Investigators} and {Schuyler Jones}, W. and Iris Baumgartner and Hiatt, {William R.} and Gretchen Heizer and Conte, {Michael S.} and White, {Christopher J.} and Berger, {Jeffrey S.} and Peter Held and Katona, {Brian G.} and Mahaffey, {Kenneth W.} and Lars Norgren and Juuso Blomster and Marcus Milleg{\aa}rd and Craig Reist and Patel, {Manesh R.} and Fowkes, {F. Gerry R.} and Jill Belch",
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EUCLID Trial Steering Committee and Investigators, Schuyler Jones, W, Baumgartner, I, Hiatt, WR, Heizer, G, Conte, MS, White, CJ, Berger, JS, Held, P, Katona, BG, Mahaffey, KW, Norgren, L, Blomster, J, Millegård, M, Reist, C, Patel, MR & Fowkes, FGR 2017, 'Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease', Circulation, vol. 135, no. 3, pp. 241-250. https://doi.org/10.1161/CIRCULATIONAHA.116.025880

Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease. / EUCLID Trial Steering Committee and Investigators; Schuyler Jones, W.; Baumgartner, Iris; Hiatt, William R.; Heizer, Gretchen; Conte, Michael S.; White, Christopher J.; Berger, Jeffrey S.; Held, Peter; Katona, Brian G.; Mahaffey, Kenneth W.; Norgren, Lars; Blomster, Juuso; Millegård, Marcus; Reist, Craig; Patel, Manesh R.; Fowkes, F. Gerry R. (Lead / Corresponding author).

In: Circulation, Vol. 135, No. 3, 17.01.2017, p. 241-250.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease

AU - EUCLID Trial Steering Committee and Investigators

AU - Schuyler Jones, W.

AU - Baumgartner, Iris

AU - Hiatt, William R.

AU - Heizer, Gretchen

AU - Conte, Michael S.

AU - White, Christopher J.

AU - Berger, Jeffrey S.

AU - Held, Peter

AU - Katona, Brian G.

AU - Mahaffey, Kenneth W.

AU - Norgren, Lars

AU - Blomster, Juuso

AU - Millegård, Marcus

AU - Reist, Craig

AU - Patel, Manesh R.

AU - Fowkes, F. Gerry R.

AU - Belch, Jill

PY - 2017/1/17

Y1 - 2017/1/17

N2 - Background: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.Methods: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding.Results: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months.Conclusions: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.

AB - Background: In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.Methods: The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding.Results: Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months.Conclusions: After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.

KW - lower extremity revascularization

KW - peripheral artery disease

KW - ticagrelor

KW - vascular intervention

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U2 - 10.1161/CIRCULATIONAHA.116.025880

DO - 10.1161/CIRCULATIONAHA.116.025880

M3 - Article

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SP - 241

EP - 250

JO - Circulation

JF - Circulation

SN - 0009-7322

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EUCLID Trial Steering Committee and Investigators, Schuyler Jones W, Baumgartner I, Hiatt WR, Heizer G, Conte MS et al. Ticagrelor Compared with Clopidogrel in Patients with Prior Lower Extremity Revascularization for Peripheral Artery Disease. Circulation. 2017 Jan 17;135(3):241-250. https://doi.org/10.1161/CIRCULATIONAHA.116.025880